Differential regulation of antiviral T-cell immunity results in stable CD8+ but declining CD4+ T-cell memory

Nat Med. 2001 Aug;7(8):913-9. doi: 10.1038/90950.


Emerging evidence indicates that CD8+ and CD4+ T-cell immunity is differentially regulated. Here we have delineated differences and commonalities among antiviral T-cell responses by enumeration and functional profiling of eight specific CD8+ and CD4+ T-cell populations during primary, memory and recall responses. A high degree of coordinate regulation among all specific T-cell populations stood out against an approximately 20-fold lower peak expansion and prolonged contraction phase of specific CD4+ T-cell populations. Surprisingly, although CD8+ T-cell memory was stably maintained for life, levels of specific CD4+ memory T cells gradually declined. However, this decay, which seemed to result from less efficient rescue from apoptosis, did not affect functionality of surviving virus-specific CD4+ T cells. Our results indicate that CD4+ T-cell memory might become limiting under physiological conditions and that conditions precipitating CD4+ T-cell loss might compromise protective immunity even in the presence of unimpaired CD8+ T-cell responses.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoptosis / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Histocompatibility Antigens Class I / chemistry
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class II / chemistry
  • Histocompatibility Antigens Class II / immunology
  • Immunologic Memory*
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data


  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II