Types of T Cells

Why This Matters

T cells represent the adaptive immune system's most versatile weapons, and understanding their distinct functions is essential for mastering immunobiology. You're being tested on more than just cell names—exams focus on how T cells recognize antigens, what effector functions they perform, and how different subsets coordinate immune responses. The interplay between helper, cytotoxic, and regulatory T cells demonstrates fundamental principles of immune activation, tolerance, and memory that appear repeatedly in FRQs.

When you study T cell types, think about the bigger picture: antigen recognition mechanisms, effector versus regulatory functions, and innate-adaptive immune bridging. Each T cell subset exists because the immune system faces different challenges—intracellular pathogens, tumors, self-tolerance, and rapid recall responses. Don't just memorize which cell does what—know why that function matters and how it connects to the broader immune response.

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Effector T Cells: Direct Action Against Threats

These T cells carry out the immune system's attack functions, either by killing target cells directly or by activating other immune cells to respond. Their effector functions depend on recognizing antigens presented by MHC molecules and delivering targeted responses.

CD4+ T Helper Cells (Th Cells)

• Orchestrate immune responses by activating B cells, CD8+ T cells, and macrophages through cytokine secretion and direct cell contact
• Differentiate into specialized subsets—Th1 cells target intracellular pathogens, Th2 cells combat parasites, and Th17 cells fight extracellular bacteria and fungi
• Recognize antigens via MHC class II molecules, which restricts their activation to professional antigen-presenting cells

CD8+ Cytotoxic T Lymphocytes (CTLs)

• Directly kill infected or cancerous cells by recognizing antigens presented on MHC class I molecules, which are expressed by all nucleated cells
• Induce apoptosis through perforin and granzymes—perforin creates pores in target membranes while granzymes enter and trigger programmed cell death
• Essential for viral clearance and tumor surveillance, making them a focus of cancer immunotherapy research

T Follicular Helper Cells (Tfh Cells)

• Specialized CD4+ subset that supports B cell responses in germinal centers, promoting antibody production and affinity maturation
• Secrete IL-21 and IL-4, which drive B cell differentiation, class switching, and the generation of high-affinity antibodies
• Critical for humoral immunity—without Tfh cells, long-lived plasma cells and memory B cells cannot form effectively

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Regulatory T Cells: Maintaining Balance

The immune system must attack pathogens without destroying healthy tissue. Regulatory cells suppress excessive responses and maintain self-tolerance, preventing autoimmunity and immunopathology.

Regulatory T Cells (Tregs)

• Suppress excessive immune responses to prevent autoimmunity and limit tissue damage during infection
• Express the transcription factor FoxP3, which is essential for their development and suppressive function—FoxP3 mutations cause severe autoimmune disease
• Maintain peripheral tolerance by inhibiting self-reactive T cells that escape thymic selection

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Memory T Cells: Long-Term Protection

After an infection resolves, most effector T cells die, but a subset persists to provide rapid protection upon re-exposure. Memory formation is the basis of vaccine-induced immunity and explains why second infections are often milder.

Memory T Cells

• Provide rapid, robust responses upon antigen re-encounter, responding faster and more powerfully than naïve T cells
• Exist as two main subsets—central memory T cells (Tcm) circulate through lymphoid organs, while effector memory T cells (Tem) patrol peripheral tissues
• Essential for vaccine efficacy, as vaccines work by generating memory cells without causing disease

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Unconventional T Cells: Bridging Innate and Adaptive Immunity

Some T cells don't follow classical rules—they recognize non-peptide antigens or respond rapidly like innate immune cells. These populations blur the line between innate and adaptive immunity, providing early defense while adaptive responses develop.

Natural Killer T Cells (NKT Cells)

• Recognize lipid antigens presented by CD1d molecules, not MHC—this allows them to detect microbial lipids and stressed cell membranes
• Respond rapidly with cytokine production and cytotoxicity, functioning within hours rather than the days required for conventional T cell activation
• Regulate both tumor immunity and autoimmunity, making them potential therapeutic targets

Gamma Delta T Cells (γδ T Cells)

• Express a unique TCR composed of γ and δ chains instead of the conventional α and β chains, allowing recognition of diverse antigens including phosphoantigens and stress molecules
• Concentrated at mucosal surfaces and epithelial barriers, where they provide first-line defense against pathogens
• Contribute to tissue repair and wound healing in addition to antimicrobial functions

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Quick Reference Table

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Self-Check Questions

1. Which two T cell types can directly kill target cells through cytotoxic mechanisms, and what molecules do they use to induce apoptosis?

2. Compare and contrast how CD4+ Th cells and Tfh cells support immune responses—what is the key functional difference between them?

3. A patient with a FoxP3 mutation develops severe autoimmune disease. Which T cell type is defective, and why does this mutation cause autoimmunity?

4. If an FRQ asks you to explain why a second exposure to a pathogen produces a faster immune response, which T cell type should you discuss, and what are its two main subsets?

5. Both NKT cells and γδ T cells are described as bridging innate and adaptive immunity. What characteristic of antigen recognition do they share that distinguishes them from conventional T cells?