Mycobacterium tuberculosis is a major human pathogen and the existing tuberculosis (TB) vaccine, BCG, is ineffective at preventing its transmission. Understanding the cellular response to pulmonary immunization will inform the development of more effective TB vaccines. We have developed a novel TB vaccine, rIAV PR8.p25, expressing the M. tuberculosis CD4⁺ T cell epitope, Ag85B_240-254 (p25) that protects mice against M. tuberculosis infection. The chemokine receptor, CXCR3, on T cells contributes to their recruitment to the lungs in response to its ligands, CXCL-9, -10 and -11 that are highly expressed during M. tuberculosis-infection in the lung, and we have investigated its role in the host T cell response to the PR8.p25 vaccine.  Using CXCR3 reporter mice, we showed that CXCR3 was expressed by the majority of CD4⁺ T cells recruited to the lung in response to PR8.p25 immunisation, including vaccine-specific T cells. To determine if CXCR3 was essential for this T cell response, CXCR3-deficient mice were immunized with PR8-p25. There was no initial reduction in the recruitment of p25-specific CD4⁺ T cells into the lungs, and after contraction of the CD4⁺ T cell response, the CXCR3-deficient mice retained more p25-specific memory CD4⁺ T cells in the lungs than WT mice. To analyse further the role of CXCR3 in the p25-specific T cell response, we crossed CXCR3-deficient mice with TCR-transgenic P25 mice, specific for p25 (CX3xP25). We adoptively transferred T cells from P25 and CX3xP25 mice to WT hosts and found that immunisation with PR8.p25 resulted in reduced recruitment of CXCR3-deficient P25 T cells to the lungs than WT CD4⁺ T cells at early time-points. These data indicate that CXCR3 promotes but is not essential for CD4⁺ T cell recruitment into the lungs in response to pulmonary immunization with the rIAV TB vaccine.

Support: NHMRC and R L Cooper Foundation