CD4(+) T cells confer anxiolytic and antidepressant-like effects, but enhance fear memory processes in Rag2(-/-) mice

Stress. 2016 May;19(3):303-11. doi: 10.1080/10253890.2016.1191466.


Accumulating evidence supports a role of T cells in behavioral stress responsiveness. Our laboratory previously reported that lymphocyte deficient Rag2(-/-) mice on a BALB/c background display resilience to maladaptive stress responses when compared with immune competent mice in the predator odor exposure (POE) paradigm, while exhibiting similar behavior in a cued fear-conditioning (FC) paradigm. In the present study, Rag2(-/-) mice on a C57BL/6 background were assessed in the same behavioral paradigms, as well as additional tests of anxiety and depressive-like behavior. Furthermore, the effects of naïve CD4(+ ) T cells were evaluated by adoptive transfer of functional cells from nonstressed, wild-type donors to Rag2(-/-) mice. Consistent with our prior results, Rag2(-/-) mice displayed an attenuated startle response after POE. Nevertheless, reconstitution of Rag2(-/-) mice with CD4(+ ) T cells did not modify startle reactivity. Additionally, in contrast with our previous findings, Rag2(-/-) mice showed attenuated fear responses in the FC paradigm compared to wild-type mice and reconstitution with CD4(+ ) T cells promoted fear learning and memory. Notably, reconstitution with CD4(+ ) T cells had anxiolytic and antidepressant-like effects in Rag2(-/-) mice that had not been previously stressed, but had no effect after POE. Taken together, our results support a role of CD4(+ ) T cells in emotionality, but also indicate that they may promote fear responses by enhancing learning and memory processes.

Keywords: Adaptive immunity; anxiety; depression; fear memory; lymphocytes; startle reactivity.

Publication types

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

MeSH terms

  • Animals
  • Anxiety / physiopathology*
  • CD4-Positive T-Lymphocytes / physiology*
  • DNA-Binding Proteins / genetics*
  • Depression / physiopathology*
  • Emotions / physiology
  • Fear / physiology*
  • Memory / physiology*
  • Mice
  • Mice, Knockout
  • Reflex, Startle / physiology


  • DNA-Binding Proteins
  • Rag2 protein, mouse