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Differentiation and functions of T cell subsets

T R Mosmann1, L Li, H Hengartner

  • 1Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Canada.

Ciba Foundation Symposium
|January 1, 1997
PubMed
Summary

CD8+ T cell subsets Tc1 and Tc2 exhibit similar cytotoxic functions and delayed type hypersensitivity (DTH) responses, irrespective of their distinct cytokine profiles. Cytokine combinations can unpredictably influence CD8+ T cell differentiation.

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Area of Science:

  • Immunology
  • Cellular Biology
  • Cytokine Signaling

Background:

  • CD8+ T effector cells comprise subsets like Tc1 and Tc2, differing in cytokine secretion (e.g., gamma-interferon for Tc1, interleukins 4 and 5 for Tc2).
  • Despite cytokine differences, Tc1 and Tc2 cells share functions such as perforin- and Fas-dependent cytotoxicity and induction of delayed type hypersensitivity (DTH) reactions.
  • CD8+ T cells may produce lower cytokine levels than CD4+ T cells due to antigen-presenting cell killing, a phenomenon influenced by stimulation frequency and perforin expression.

Purpose of the Study:

  • To investigate the relationship between CD8+ T cell cytokine patterns and their functional outcomes, specifically DTH reactions.
  • To explore the complex effects of combined cytokines on CD8+ T cell differentiation.
  • To identify conditions where specific cytokines (interleukins 4, 10, 12) exert opposing influences on CD8+ T cell development.

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Main Methods:

  • Analysis of cytokine profiles (gamma-interferon, interleukins 4 and 5) in Tc1 and Tc2 cell subsets.
  • Assessment of perforin- and Fas-dependent cytotoxicity.
  • Induction and measurement of delayed type hypersensitivity (DTH) reactions, including edema and granulocytic infiltration.
  • Multiparameter analysis of seven cytokines, testing all combinations for their effects on CD8+ T cell differentiation.

Main Results:

  • CD8+ T cell cytokine patterns did not correlate with the induction of DTH reactions, as Tc1 cells deficient in cytokine synthesis still induced similar DTH levels.
  • The in vivo expression of characteristic Tc1 (gamma-interferon) and Tc2 (interleukins 4 and 5) cytokines was observed during DTH reactions.
  • Combinatorial cytokine effects on CD8+ T cell differentiation were complex, with some outcomes unpredictable from individual cytokine functions.
  • Specific conditions were identified where interleukins 4, 10, and 12 demonstrated opposing effects on CD8+ T cell differentiation.

Conclusions:

  • CD8+ T cell function, including DTH, is not solely dictated by their cytokine secretion profile.
  • Complex cytokine mixtures, rather than individual cytokines, play a critical role in shaping CD8+ T cell differentiation.
  • Understanding these complex cytokine interactions is crucial for deciphering normal immune responses and developing targeted immunotherapies.